Current knowledge suggests that the function of te cerebral cortex depends in large part on synaptic interactions between its constituent cells, and so to understand how the cortex functions, it is first necessary to identify its constituent neurons and to determine the numbers and types of synapses linking them with each other and with neurons in other parts of the brain. The aims of this proposal are to provede this kind of specific information which is needed to decipher the complex synaptic circuitry of the cerebral cortex. Specifically, it is intended to identify and quantify synapses between labeled thalamocortical (and cortico-cortical) axon terminals and identified neurons in mouse primary somatosensory cortex. Presynaptic elements will be labeled by lesion-induced degeneration, which in this system allows synapses of thalamocortical and cortico-cortical afferents to be quantified, or, by EM autoradiography. Neurons postsynaptic to these afferents will be identified by (1) the Golgi-EM gold-toning method, (2) a new method using the retrograde transport of horseradish peroxidase to completely fill neurons, or (3) for some non-spiny neurons, by tracing them in serial thin sections. An additional aim is to identify intrinsic cortical synaptic connections by examining the local axonal projections of identified neurons which receive known amounts of thalamocortical and/or cortico-cortical synapses. Serial thin sections will be examined in all phases of the proposed studies because this is the only method by which all the synaptic relationships of one portion of an axon or dendrite can be conclusively demonstrated, enabling both the type and frequency of synapses to be determined. This information is a necessity for the elaboration of accurate theoretical models of cerebral cortical function. In mouse primary somatosensory cortex the neuronal types typical of mammalian cerebral cortex are organized into functional columns similar to those observed in many regions of the subprimate and primate neocortex. For this reason, the proposed studies are expected to uncover principles of cortical functional organization which may be generalized to other cortical systems in other species including man.